This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Producing an effective vaccine for HIV infection remains difficult, largely due to the tremendous diversity of HIV strains in the population, which has resulted from the viruses ability to mutate frequently and recombine with other strains and continually express new envelope sequences that evade the initial host immune response. Furthermore, native, replication competent vaccine candidates or vectors (and live virus) usually generate and express env proteins on the surface of viruses with a heavily glycosylated "glycan shield" that prevents the host immune system from recognizing key epitopes. To date, all vaccine candidates and trials have involved only one or two envelope sequences of HIV or SIV, which are usually from a clonal env sequence, and these induce poor immune responses against env, the primary molecule responsible for infecting cells. In fact very few monoclonal antibodies have been discovered that neutralize env in wild type viruses. However, our collaborators at Case Western Reserve have developed a new, yeast-based cloning technique that can incorporate numerous different env sequences in a SHIV and they have produced new clade C SHIVs for testing in macaques. We have started this project and will have in vivo data on the transmissibility of these new viruses within this year.